- Squatting forces blood from the legs back to the heart: Increases preload Source
- MVP causes and mid systolic click and late systolic murmur.
old test was urinary 5-hydroxyindoleacetic acid.
Hormone secreting cells in the pituitary are acidophils and basophils. Acidophils are somatotrophs and lactotrophs.
IGF has the longer half life; therefore it's used as a screening test for acromegaly. GH has a short half life and levels fluctuate throughout the day so it's not the first test in screening.
### Summary of enzymes involved
AOSD is a diagnosis of exclusion;
When to suspect: Any adult with daily or twice daily fever spikes with evanescent, salmon pink, non pruritic rash (which disappears with settling fever)
Also, arthritis, #lymphadenopathy , sore throat and #splenomegaly
Rash disappears during afebrile periods; present on trunk and extremities. Non pruritic.
CRP markedly elevated.
Investigations: neutrophil leukocytosis, thrombocytosis, anaemia, elevated transaminases; very high ferritin
| Still's | Very high ferritin; not seen in other diseases |
| SLE | ANA is positive; ANA not positive in AOSD |
Characteristic feature: Fusion of wrist joints;
Rash mostly affects chest and thighs.
Pancytopaenia with bleeding manifestations: purpura, easy bruising, mucosal bleeds. (low fibrinogen levels seen)
also ⬆liver enzymes, ⬆Triglycerdies ⬆LDH and ⬇Na levels,
Management: High dose IV corticosteroids or High dose IVIG +/- cylcosporine / cyclophosphamide.
Caused by rickettsia : obligate intracellular gram -ve bacteria with varying morphology
Note: Ticks Vs. fleas : ticks are much larger and have eight legs. Ticks aren't involved in typhus.
Chiggers aren't insects. They are mites.
Epidemic typhus causes the most severe clinical presentation -> severe epidemic typhus may develop gangrene, leading to a loss of digits, limbs, or other appendage.
- Thrombosis: **renal vein thrombosis is a recognised complication of nephrotic syndrome** (occuring in 33%)
[!INFO] Presentation of renal vein thrombosis:
- Acute: flank pain, gross / microscopic haematuria, enlarged kidney on USS, elevated LDH with normal liver enzymes.
- Chronic: Asymptomatic; Usually incidentally found on investigation of pulmonary embolus.
[!INFO] 95% of TTP is immune mediated
Only a tiny percetage is hereditary.
Mnemonic; Transfer
6. immunosuppresion
7. neurology - uraemai -> CNS depression, ⬇ seizure threshold, asterexis, tremmor, myoglonus, axiety + depression, impaired cognition
1. Autonomic dysfunction : increased cirulating catecholamines -> alpha receptor down regulation.
2. Peripheral - median nerve compression due to Beta 2 microglobulin amyloidosis.
3. Advaned uraemia -> symmetrical polyneuropathy.
- They are peptides *similar in structure to insulin* and are **produced in the liver.**
- **IGF-I peaks in puberty** and it's main role is skeletal and cartilage growth. It is stimulated by GH.
However, crystals can precipitate and cause nephropathy. Prevented by adequate hydration.
Neurotoxicity is rare bu[[]]t can cause delirium, tremors, hallucinations and if severe delerium and coma.
Pan-systolic - ventricle leaks to a lower pressure chamber or vessels - MR, TR, VSD
Mid diastolic
Mid diastolic - MS, TS,
CYP2D6 and CYP3A4 are hepatic drug metabolism pathways / enzymes
#2019BSQ-OCT/Q14
"The first pass effect is a phenomenon in which a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation." Basically 👇🏽
First pass effect - drug gets metabolized at a non target organ so that affective dose at the target organ is reduced. Commonest site for this to happen is the liver.
P-glycoproteins in the gut can cause efflux of drugs, reducing absorption. Another example of first pass effect.
First pass metabolism varies between people.
First pass effect is significant only if the liver metabolizes the drug rapidly.
So even though the following are completely eleminated by the liver, since the rate of elimination is low, first pass effect is not significant
e.g. for diazepam, phenytoin, theophylline, warfarin.
In cirrhosis, first pass metabolism is reduced because of
📑More drugs with high FP metabolism:
First pass metabolism occurs in the 📑gut for 📑 benzylpenicillin (penicillin G) and insulin and
in the liver for propranolol, lignocaine, chloromethiasole and GTN.
Phase 1: Oxidation, reduction and hydrolysis reactions - make the drug more polar and water soluble. Fa
Geriatric patients have reduced phase 1 reaction rates.
Phase 1 is catalyzed by the membrane-bound cytochrome P450.
Phase 2: glucuronidation, acetylation and sulfation - make a drug even more soluble by conjugation with another group.
Acetylation is one example. Patients can be slow or fast acetylators. [[Tuberculosis#Isoniazid]]
Phase 2 reactions occur on a metabolite formed by a phase I reaction that is still not adequately hydrophilic.
Phase II reactions result in the formation of readily excreted, less active,nontoxic substances.
They occur within hepatocytes cytoplasm.
$$ Therapeutic; index = \frac{LD_50}{ED_50} $$
LD50 = median lethal dose
ED50 = median effective dose

#2020SBR-NOV/Q03
Cardiac glycoside - Found in [[Plant toxins|Kaneru]]
Classified as Other in Vaughan Williams anriarrhythmic classification.
[[VaughanWilliamsClassificationAntiarrhythmics.png]]
Cardiac glycosides reversibly inhibit the sodium-potassium-ATPase, causing an increase in intracellular sodium and a decrease in intracellular potassium.
Indications and mechanism of action
Overall effects : increased contractile velocity (increased contractility) and decreased heart rate.
In patients with HF, digoxin also inhibits sympathetic outflow and augments parasympathetic tone.
Antiarrhythmic - slows conduction through the AV node, increases vagal tone. This property is used to slow the ventricular rate in patients with persistent AF.
📑Avoid in acute coronary syndrome
[!INFO] Benign effects on the ECG:
Source
#2020GM-JUL/Q02
These effects occur at therapeutic doses
- Downsloping ST depression - 'salvador dali' or 'reverse tick' appearance.
- Biphasic T waves.(negative deflection followed by positive) (or even flattened of inverted T waves)
- The preceding two changes are used by decreased in the atrial and ventricular refractory periods and alterations in ventricular repolorization.
- Shortening of QT interval
- Mild prolongation of the PR interval due to increased vagal tone to the AV node.
Is a water soluble drug (renally excreted) ?but has large volume of distribution - Distributed within skeletal and cardiac muscle. Patients with low muscle mass (elderly) or renal failure will need loading dose adjustment.
Drug has a large Vd. so it's makes sense that it exerts it's effects on muscle.
Acute toxicity is uncommon: Effects are
[!WARNING] Common effects of digoxin toxicity on the ECG
Other common dysrhythmias associated with digoxin toxicity include:
- Frequent PVCs (the most common abnormality), including ventricular bigeminy and trigeminy
- Sinus bradycardia
- Slow Atrial Fibrillation
- Any type of AV block (1st degree, 2nd degree & 3rd degree)
- Regularised AF = AF with complete heart block and a junctional or ventricular escape rhythm
- Ventricular tachycardia, including polymorphic and bidirectional VT
- Source
Management
See [[Psychiatric drugs]]
Source
Focal seizure = previously called partial seizures.
Focal onset aware seizure = simple partial seizure = person doesn't lose awareness of surroundings.
#2020BSQ-JUL/Q22
Carbamazepine, phenobarbital and phenytoin are "narrow spectrum" -> used mainly for focal onset seizures.
Clobazam, lamtotrigine, levetiracetam, topiramate, valproate are "broad spectrum" -> used for both focal and generalized seizures.
Ethosuximide -> used for absence seizures.
Levetiracetam: Drug of choice for partial and / or secondary generalized seizures. Non sedating.
Lamotrigine is also a first line drug for partial and generalized epilepsy. Non sedating.
Source + Bennet & Brown.
These drugs, (among others) work by blocking sodium channels.
They show 'use dependence' whereby more frequently depolarizing neurons are affected more.
Is a substrate for inducible hepatic enzymes; dose must be increasedin pregnancy!!
are used for acute management of seizure. Not for seizure prophylaxis.
However, clonazepam is used to achieve rapid control of epilepsy. (eg. When a patient with frequent seizures presents for the first time).
Special because it's useful for myoclonic, tonic clonic and absence seizures.
Low toxicity; Non sedative.
Multiple mechanisms of action:
[!TIP] Overview
Effective anti epileptic but with unpredictable pharmacology and significant toxic effects.
[!SUMMARY] Phenytoin
Phenytoin is a second line antiepileptic (now used mainly in ED settings) with narrow therapeutic window.
It has multiple side effects.
- Acute toxicity can produce motor symptoms.
- Low protein states, uraemia, and liver dysfunction predispose to toxicity.
- Gum swelling, hypertrichosis and idiosyncratic TEN are important side effects
Mechanism:
Phenytoin binds to and inhibits voltage-dependent sodium channels, which are found on both neuronal and cardiac tissue.
Cardiac effect: shortens actions potentials and prolongs refractory period between them.`
#2020BSQ-NOV/Q15
Enzyme inducer.
Valproate displaces phenytoin from bound proteins -> increased risk of toxicity.
Ethanol / Phenobarbital
Symptoms : N/V, headache,
motor effects: nystagmus, tremor, cerebellar ataxia.
10 - 20 - occasional horizontal nystagmus
20 - 30 - nystagmus+
30 - 40 - ataxia, slurred speech, tremmors, NV
40 - 50 - lethargy, confusion and hyperactivity
> 50 mg/L. - Coma and seizures
IV phenytoin can have cardiac effects;
Rare side effect of IV phenytoin : purple glove syndrome: distal oedema of limbs with necrosis.
==Phenytoin worsens primary generalized epilepsies.==
📑Phenytoin worsens absence seizures and myoclonic seizures.
Supportive; mortality rate is low.
Phenytoin is structurally related to the barbiturates.
New name is DRESS. "Drug reaction with eosinophilia and systemic symptoms.".
Occurs between 2 - 8 weeks after starting the drug.
Can occur with many drugs, including antiepileptics.
Features:
Rapid summary:
A Good overview of arachidonic acid metabolism in the context of mechanism of action of paracetamol <- lots of detail; too long to read in a hurry.
COX = cyclooxygenase
PGHS = prostaglandin synthesae = cyclooxygenase
Cyclooxygenase (COX) is the rate-limiting enzyme in prostaglandin (PG) synthesis.
COX 1 = present in most tissues; "housekeeping". Protects the gastric mucosa, kidney function, platelet activation
COX 2 = usually expressed in brain, kidney and bone. During inflammation, it is expressed in other tissues as well.
The synthesized prostaglandins bind to G protein coupled receptors to exert their effects.
The graph shows the concentration of each drug needed to reduce activity of the COX 1 and 2 enzymes by 50% (IC50).
Fever occurs due to the induction of COX-2 and subsequent increase in PGE2.
Recently a COX-3 isoform has been discovered. It was shown to be more sensitive to inhibition by paracetamol than other COXes and, so, was thought to be the target of analgesic and antipyretic effect of paracetamol; but this has been disproved.
NSAIDs have
Most NSAIDS inhibit COX-1 by competitive reversible inhibition.
COX-2 inhibition is usually irreversible.
The antiplatelet action of aspirin isn't seen with other NSAIDS.
NSAIDS other than aspirin tend to have deleterious cardiovascular effects: they can cause hypertension by interfering with macula densa function.
Paracetamol is an NSAID-like drug with antipyretic and analgesic properties but no antiinflammatory properties.
Kidney PGs are primarily local vasodilators.
In the setting of hypotension and reduced kidney perfusion from vasoconstriction stimulated by angiotensin II, norepinephrine, vasopressin, or endothelin, PG synthesis is increased to maintain kidney perfusion and minimize ischemia
PGs also increase renin secretion, antagonize the water-retentive effects of arginine vasopressin, and enhance sodium excretion (See "NSAIDs: Electrolyte complications")
NSAIDS can cause hyperkalemia, hyponatremia and oedema
Hemodynamically mediated AKI due to NSAIDs occurs via attenuation of PG-mediated renal vasodilation. In healthy patients, PGs play little role in renal hemodynamics.
Source - Katzung
[!INFO] Pharmacokinetics Vs. Pharmacodynamics
Dynamics = 'power'
Pharmacodynamics = effect drugs have on the body.
Pharmacokinetics = effect body has on drug concentrations.
#2020BSQ-NOV/Q17
$$
Bioavailability=\frac{AUC_{oral}}{AUC_{IV}}
$$
where AUC = area under the curve for drug concentration Vs. time graph.
#2020BSQ-JUL/Q20
Epic article by DeragedPhysiology
#2022BSQ Q17
Given when time-to-steady-state (4-5 half lives) would be too long to wait for the drug to take action.
$$Loading\space Dose = \frac{{Vd}\times{Tc}}{F}$$
Vd = volume of distribution, Tc = Target concentration, F = bioavailability
For IV drugs given by infusion,
- Dose rate (mg/hr) = dose (mg) divided by dosing interval (hrs)
- Maintenance dose rate (mg/hr) = desired peak concentration (mg/L) × clearance (L/hr)
- Loading dose = desired peak concentration (mg/L) × volume of distribution (L)
For drugs not given IV, these doses need to be divided by the bioavailability.
The equation describing the half life of a drug:
$$
\large{C_t = C_0exp\frac{-CL_{tot}}{V_d}t}
$$
where 'exp' means e to the power of'.
alternative form
$$
\large{C_t = C_0.e^{-kt}}
$$
The exponent part in the equation above is the elimination rate constant.
CLtot = total clearance (i.e plasma volume which contains the amount of drug removed by all systems in a unit time)
$$
\frac{-CL_{tot}}{V_d} = \text{elimination rate constant} = k_{el}
$$
[!INFO] Half life depends on clearance and volume of distribution
$$
half\space life = \frac{0.693}{K_{el}}
$$
$$
\Large{Therapeutic\space Index=\frac{LD_{50}}{ED_{50}}}
$$
Higher therapeutic index => less toxic drug (high LD or low ED)
Lower therapeutic index => more toxic drug (low LD or high ED)
#2020BSQ-NOV/Q15
[!INFO]
Extraction ratio : Hepatic extraction ratio ... is the fraction of the drug entering the liver in the blood which is irreversibly removed (extracted) during one pass of the blood through the liver.
$$
\large Extraction\space Ratio = \frac{C_{arterial} - C_{venous}}{C_{arterial}}
$$
Protein binding affects hepatic extraction ratio because hepatocytes have access only to the unbound form of the drug.
Therefore, the equation above is equivalently represented as
$$
\large E_H = \frac{fu\times Cl_{int}}{Q_{H}+fu\times Cl_{int}}
$$
- (EH = hepatic extraction ratio)
- (Cl = intrinsic clearance)
- Intrinsic clearance is the intrinsic ability of the liver to remove (metabolise) the drug in absence of restrictions imposed on drug delivery to the liver cell by blood flow or protein binding.
- It basically expresses how powerful the liver enzymes are at removing a drug.
- Fu - Fraction of unbound drug in the plasma
- QH - hepatic blood flow
Finally we have the following equation for hepatic clearance: (ClH)
$$
\large Cl_{H} = Q_{H} \times \frac{fu\times Cl_{int}}{Q_{H}+fu\times Cl_{int}}
$$
So, we can see that hepatic clearance is affected by
- Hepatic blood flow
- Unbound fraction of the drug
- Intrinsic ability of the liver to metabolize the drug
[!INFO] The upshot
Drugs with low intrinsic clearance will have "intrinsic limited" clearance
Drugs with high intrinsic clearance will have "flow limited" clearance.
Extraction ratio for all drugs decreases with increasing hepatic flow.
| Low extraction ratio drugs | High extraction ratio drugs |
|---|---|
| Flow independent | Flow dependent |
| Warfarin, phenytoin | Morphine, GTN, propranolol, verapamil |
| Lignogaine |
In liver failure,
| Synthetic corticosteroid | Natural |
|---|---|
| Predni and Methyl predni | |
| Dexamethasone | |
| betamethasone | |
| Triamcinolone | |
| Little mineralocorticoid or andro/estrogenic activity | |
| Therefore, they suppress HPA axis and Cause cushing | |
| Mainly glucocorticoid activity | |
clinically desirable effects of steroids appear to result primarily from transrepression, which results in the decreased production of proinflammatory proteins
[!INFO] Glucocorticoids have non-genomic effects as well
"Nongenomic effects of glucocorticoids include rapid, nonspecific interactions of glucocorticoids with cellular membranes, nongenomic effects medicated by cytosolic glucocorticoid receptors, and specific interactions with membrane-bound glucocorticoid receptors"
[!INFO] Irriversible side effects
With the exception of cataracts, a potential acceleration in atherosclerotic vascular disease, and bone effects (osteoporosis and osteonecrosis), all glucocorticoid toxicity is at least partially reversible over time with glucocorticoid discontinuation
Pathologic Increase in aldosterone can cause salt and water retention. But after a few days (or about 3Kg gain in weight), diuresis occurs. This is in response to
- increased ANP secretion
- Pressure natriuresis - kidney decreases Na resorption in response to increased perfusion pressure
- Decreased DCT resorption of Na via downregulation of thiazide sensitive sodium chloride co-transporter. ^c2b35e
https://www.ncbi.nlm.nih.gov/books/NBK553990/table/ch31.Tab1/
Antifolate drug;
Absolute contraindications: pregnancy, breast feeding, alcoholism and alcoholic liver disease, any other type of chronic liver disease, leukopenia / thrombocytopaenia, anaemia, bone marrow hypoplasia.
For some drugs, precise mechanism is unknown or several mechanisms are suspected.
See table in up to date
Alteration of sodium currents is the most common mechanism of action of available antiseizure medications.
Type of receptor blockade may explain why some drugs are more effective for particular types of seizures.
Phenytoin , phenobarbitone and carbamazepine are some of the oldest antiseizure medications. - Newer drugs have better pharmacokinetics.
Binds Na Channels
This binding extends the inactivated phase and inhibits the generation of rapid action potentials when the cell is experiencing incoming depolarizing trains
#TODO
#2023SBR Q23
Fosphenytoin is the prodrug. Superceded Phenytoin for IV use. (? Not really in SL)
Block Na channels, like carbamazepine.
Inhibits synaptic transmission.
And others...
focal and generalized seizures
for status epilepticus
and as a second-line agent for patients with mixed seizures
95% protein bound ; renal failure impairs protein binding.
Valproate is another highly protein bound drug which ?may displace Phenytoin and increase its plasma levels.
potent, broad spectrum CYP and glucuronidation inducer.
Side effects:
Systemic: gingival hypertrophy, body hair increase, rash, folic acid depletion, reduced bone density (enzyme induction -> incr. Vitamin D catabolism)
Stevens-Johnson / TEN (commoner in south Asia!)
[!INFO] Ataxia
"ataxia" - disordered
Neurologic :
confusion
Slurred speech, ataxia, diplopia (all involving the head region)
Neuropathy
[!TIP] left Side - Inhibitors; Right side - INDUCERS,
| Strong inhibitors | Strong inducers |
|---|---|
| Clarithromycin | Carbamazepine |
| Itrakonazole, ketoconazole | Phenytoin |
| Voriconazole | Fosphenytoin |
| Phenobarbital | |
| Rifampicin |
| Moderate inhibitors | Moderate inducers |
|---|---|
| Amiodarone | Bosentan |
| Aprepitant/ fosaprepitatnt | Dexamethasone |
| Cimetidine | St. John's wort |
| Diltazem | |
| Erythromycin | |
| Fluconazole | |
| Verapamil |
The protein bound from and free form of drugs are in equilibrium. The bound form acts as a reservoir. The unbound form is active and also subject to elimination.
The free, unbound portion of a drug can be very small. (1%).
The most important protein which binds drugs is albumin.
Albumin binds many acidic drugs - warfarin, NSAIDS, Sulfonamides.
and fewer basic drugs (TCA, chlropromazine).
For most drugs at therapeutic concentration, the carrier proteins are very far from saturated.
At these concentrations, bound fraction does not changes with drug concentration.
However, tolbutamide almost completely saturates proteins at therapeutic level. So increasing dose increases the free proportion disproporionately. (Tolbultamide is a nonantimicrobial sulfonamide)
Sulfonamides have very high affinity so they occupy about 50% of the binding sites on albumin. This allows sulfonamides to significantly displace other protein bound drugs.
From DerangedPhysiology:
Selected drugs which are highly protein bound
Source
Initially developed as antibacterials; not used much now for that role (because of resistance) except for
Non antibacterial sulfonamides
There are antimicrobial and non antimicrobial sulfonamides: There's a large list!
List
Sulfonamide-containing nonantimicrobial agents (Table 1) include agents from therapeutic classifications such as thiazide and loop diuretics, carbonic anhydrase inhibitors, nonsteroidal anti-inflammatory drugs, sulfonylureas, antiretrovirals, and 5HT-3 receptor agonists
In the general population, approximately 3–8% of patients are reported to experience a sulfonamide allergy.
Stevens-Johnson syndrome can occur.
[!INFO] Allergy
Although many types of drugs have the NH2-SO2 sulpha group and are therefore technically 'sulfa-drugs', they don't have some additional group which are responsible for the allergies caused by the antibacterial sulphonamides. Therefore, cross reactivity and allergy risk is low.
The nonantimicrobial sulfonamides do not undergo metabolism to the N4-hydroxylated metabolite associated with SJS and will not bind to IgE at the N1 position and, therefore, are unlikely to cause cross-reactivity, even in patients who have experienced type 1 hypersensitivity or serious non-type-1 hypersensitivity reactions to sulfonamide antimicrobial agents.
#2020BSQ-JUL/Q19
📑 A few known drugs show zero order / 0 order kinetics.
==Most drugs show first order kinetics==.
ChatGPT: (verified)
Important implications for saturation kinetics:
Illustration of the difference of variation in plasma concentration between zero and first order kinetics:
Phenytoin is the classical poster child for non-linear elimination kinetics, because the enzyme saturation point is reached somewhere in the middle of the therapeutic concentration range - Deranged Physiology
#2018BSQ-OCT/Q02
Efficacy is the maximum effect that a drug can exert.
Potency is the concentration/dose of drug required to exert 50% of it's maximal effect.
Source
A has higher efficacy than B.
But the dose at which 50% of maximum drug effect is achieved for Both A and B are similar. (?so similar potency?)
The concept above is therapeutic efficacy.
Pharmacological efficay (also called Intrinsic efficacy) is
is the drug's maximal efficacy as a fraction of the maximal efficacy produced by a full agonist of the same type acting through the same receptors under the same conditions
A and B have the same maximum effect (i.e same efficacy) but A achieves this at a lower dose; Therefore, A is more potent.

Drug B is more potent than Drug A. Drug A and B have the same efficacy.
However, A has a steeper dose response curve so it requires a smaller increase in dose than B to achieve maximum effect.
#2022SBR-MAY Q08
[!TIP] Dihydropyridines end with 'pine'
Calcium channel blockers block the voltage gated L type calcium channels on cells, inhibiting calcium entry.
They show 'use dependence' so that they most affected tissues are heart and smooth muscle.
In smooth muscle, they cause relaxation -> predominant clinical effect is arteriolar dilation and coronary artery dilation; lowers blood pressure but also causes oedema.
In the heart, they have delay conduction and have a negative inotropic effect.
Site of action:
Most dihydropyridines affect smooth muscles more than the heart.
Ditiazem (nondihydropyridine) has intermediate action.
Verapamil acts mainly on the heart.
[!INFO] Specificity of heart Vs. smooth muscle lies along a spectrum
- CCBs acting on smooth muscle cause reflex tachycardia (and oedema).
- Diltiazem does not affect heart rate.
- Verapamil has negative chronotropic and inotropic effects.
Dihydropyridine structure kind of looks lika a smooth muscle cell.
Side effects are extensions of the pharmacological action.
Hyperglycemia is a side effect of CCB overdose which helps differentiate this from beta blocker overdose.
#2022SBR-MAY Q14
Caused by TSST-1 toxin produced by staph aureus.
Toxin causes cytokine release which leads to rapid (48 hr) development of clinical features:
Treatment:
Occurs in children < 5 years old.
Exfoliatin produced by Staph aureus causes intrapidermal separation of the skin (at level of stratum corneum) resulting in flaccid blisters. Benign condition. Only requires flucloxacillin.
[!INFO] Mast cells
Previously called IgA vasculitis.
Symptoms:
| False negative | False positive |
|---|---|
| Incorrect technique | TB infection (but not disease) |
| Immunosuppression (HIV, lymphoma, late CKD) | Past disease |
| viral infections | Non tuberculous mycobacteria |
| Malnutrition | |
| Vaccination with live viral vaccine | |
| Sarcoidosis (sarcoid. granulomas interfere) | |
| Miliary TB (due to anergy) | |
We are concerned with the true positive rate and true negative rate of a test.
[!INFO] interpretation of sensitivity and specificity
SNOUT and SPINS
- Sn: Sensitive test rules out the disease when it is negative.
- Sp: specific test rules in a disease when it is positive.
This part is intuitive:
[!INFO] Type 1 Vs type 2 error
- When the boy cried wolf for the first time and the villagers believed him : type 1 error
- When the boy cried wolf for the second time, the villagers didn't believe him : type 2 error.
[!INFO] prerequisite knowledge:
- What is parametric statistics?
- The branch of statistics which assumes that underlying population characteristic follows a known distribution which can be described with certain parameters. The most common such distribution is the normal distribution.
- But other distributions can also be assumed in parametric statistics. (The chi squared distribution, the poisson distrubition etc)
[!WARNING] Wilcoxon rank sum test is the same as Mann-whitney U test
Mnemonic: Both have U in the name
Nominal = categorial
No sense of order.
Frequency or percentage is used to summarise.
Ordinal:
Have an order.
But the interval between values is unequal.
Interval / ratio
Things that can be measured
- The probability of not making a type 2 error
Or equivalently- the probability of rejecting the null hypothesis when it is false.
The probability that a study will detect a difference in measurement between two groups when such a difference actually exists, given a pre-set p alpha and sample size.
| Chloride responsive | Chloride resistant |
|---|---|
| GI H+ loss | HCO3- retention |
| contraction alkalosis | Intracellular H+ shift |
| Diuretic therapy | Hyperaldosteronism |
| Post hypercapnia | Barter syndrome |
| Cystic fibrosis | Gitelman syndrome |
| Exogenous alkalotic | |
[!INFO] Pendrin
Is a key transport protein involved in pathogenesis.
The transcellular shifts in K+ caused by acid base changes.
Basis: In acidosis, about half the H+ is buffered intracellularly. To maintain electroneutrality, intracellular K+ moves outwards into the ECF.
[!INFO] Hypoaldosteronism
In patients with hypoaldosteronism, for example, the mild metabolic acidosis is primarily due to the associated hyperkalemia
UpToDate